M.A.
Psychology
Kenneth A. Brown
MULTI-UNIT ACTIVITY IN THE HYPOTHAlAMUS:
EFFECTS OF GLUCOSE
i
MUlti-unit and EEG activity were recorded fram the lateral, ventromedial, and varibus other hypothalamic
.
~reas
in
chronically prepared cats while glucose solutions were injected or infused intravenously.
Injections of insulin were
given and distension of the stomach was performed on sorne
preparations.
multi-uni~
Glucose injections and infusions diminished
activity in the lateral hypothalamus and in-
creased activity in the ventromedial hypothalamus.
Sünilar
changes in activity levels were noted in other hypothalamic
areas.
Insulin
injectio~s
and stomach distension did not
markedly affect activity levels in the areas
investigat~d.
EEG effects were generally unreliable and inconsistent.
Anesthetic effects and baseline tonic activity levels at
the recording sites are discussed.
The results support the
notion that blood glucose is at least one factor in food
intake regulation and further indicate that a variety of
hypothalamic areas may be involved in such regulation.
MULTI-UNIT ACTIVITY IN THE HYPOTHALAMUS:
EFFECTS OF GLUCOSE
MULTI-UNIT ACTIVITY IN THE HYPOTHALAMUS:
EFFECTS OF GLUCOSE
by
,
..
Kenneth A. Brown
,
A thesis submitted to the facu1ty of
Graduate Studies and Research in partial
fu1fi1lment of the requirements for the
degree Master of Arts.
..
Department of Psycho1ogy
MCGi11 University
Montreal
August 1968
lOt,O
ACKNOWLEDGEMENTS
l would like to thank Dr. Ronald Melzack for his
help and encouragement and Dr. Richard Bambridge for
his technical advice and many forms of generous
assistance during the course of this research.
TABLE OF CONTENTS
Page
INTRODUCTION
,
1
METHODS
14
RESULTS
19
DISCUSSION
28
SUMMARY
35
REFERENCES
38
FIGURES 1 - 15
53
INTRODUCTION
The régulation of food intake in organisms has
interested both psycho10gists and physio10gists because
it is c1ose1y re1ated to the genera1 prob1em of motivation
and, at the same time, to the maintenance of a stable
interna1 environment in the face of an externa1 environmental flux.
The prob1ems and techniques invo1ved in
the study of feeding behavior have therefore become
increasing1y common to psycho10gy and physio10gy, and
the regu1ation of food intake has become a major field
of research in physio10gica1 psycho10gy.
Food consumption is the on1y means by which an
organism can rep1enish energy stores dep1eted by the
ongoing processes of the body.
A1though transient
imba1ances in the metabo1ic econamy may be to1erated,
the adu1t organism maintains a re1ative1y constant body
weight over long periods of time.
This balance of energy
is dependent upon the initiation offeeding activity
when energy reserves are 10w and upon the cessation of
food intake when consumption is sufficient to re1ieve
the deficit.
Impairment of the triggering of consummatory
behavior resu1ts in anorexia and 10ss of body weight whi1e
deficiencies in the satiety mechanisms produce hyperphagia
- 2 and obesity.
Factors in Regulation
Ear1y studies of hunger or feeding behavior, in this
century, emphasized the ro1e of periphera1 mechanisms in
the control of food intake (Carlson, 1912-1913, 1914;
Cannon and Washburn, 1912; Cannon, 1934).
For some
time it was be1ieved that signa1s arising from contractions
of the empty stomach are the stimuli which determine the
onset of food-seeking and consumption.
When this local
stimulation is e1iminated by fi11ing the stomach, eating
ceases.
Thus, gastric contractions were shown to corre1ate
high1y with reports of hunger in humans (Cannon and
Washburn, 1912) and with feeding behavior (Meschan and
Quig1ey, 1938).
This periphera1ist conception, however,
encountered serious difficu1ty when it was observed that
gastric denervation does not disrupt either "hunger"
(Grossman and Stein, 1948) or feeding behavior appropriate
for regu1ation (Bash, 1939; Morgan and Morgan, 1940;
Grossman!! al., 1947).
Simi1ar1y, gastrectomy does not
serious1y affect food intake regu1ation (Wangenstein and
Carlson, 1931; Tsang, 1938).
Moreover, gastric distension
was shown to be re1ative1y unimportant as a satiety cue--
- 3 -
introduction of non-nutrient bu1k to the diet (Ado1ph,
1947) or injection of food direct1y into the stomach
prior to normal feeding times (Janowitz and Grossman,
1949; Berkun et al., 1952; Share
~
al., 1952)
serious1y impair normal food intake'.
do not
Oropharyngea1
and olfactory signa1s have a1so been e1iminated as
crucial factors in regulation (Epstein and Teitelbaum,
1962), a1though such stimulation is reinforcing (Hull
~
al., 1951; Berkun et al., 1952; Miller and Kessen,
1952; Pfaffman, 1960; Teitelbaum and Epstein, 1963)
and may mediate food selection as we1l as influence
motivationa1 components of regu1ation.
Thus it is clear that periphera1 mechanisms, whi1e
necessary for the normal operation of central integrative
systems, do not exert ultimate regulatory control over
food intake.
Rather, the peripheral factors must have
their effects on central neural processes which exert
more direct control over the organism's feeding behavior.
The contributions to regu1ation made by motivational
variables have been studied in detai1, and the 1iterature
concerning the influences of early experience, food
palatability, specific hungers, drive interactions, and
- 4 other instinctive and acquired factors invo1ved in feeding
and
hunge~
have been reviewed by Hinde (1953, 1966),
Ste11ar (1954), Barnett (1956), Grossman (1967), and
Teitelb~um
(1967).
A variety of central structures are known to be
invo1ved in the control of food intake.
The importance
of these central processes is indicated by observations
that decerebrate rats (Woods, 1964), cats (Miller and
Sherrington, 1916; Bazett and Penfie1d, 1922; Bard and
Rioch, 1937), and human infants (Kirschbaum, 1951; Monnier
and Wi11i, 1953) are unab1e to regu1ate their food intake
adequate1y, a1though consummatory ref1exes remain unaffected.
Cortical contributions to regu1ation have not been studied
intensive1y, but there is evidence of cortical Mediation
of comp1ex appetitive behavior patterns in the adu1t
organism (Kirschbaum, 1951; Pribram and Bagshaw, 1953).
Remova1 of frontal cortex produces hyperphagia, at 1east
in some subjects (Watts and Fulton, 1934; Langworthy and
Richter, 1939; Richter and Hawkes, 1939; Anand et al.,
1958).
A1though the cortex is not strict1y essentia1
to regu1ated food consumption, it May participate in
the fine control of motor adjustments associated with
- 5 -
feeding and may augment the variability of responses at
the organism's disposal for accamplishing regulation
(Hess, 1957; Morgane and Kosman, 1959).
Portions of
the brainstem also appear to influence higher brain
mechanisms responsible for regulation, an idea suggested
by Sherrington (1900) and supported by studies of the
motivational effects of les ions and electrical stimulation
of the brainstem (Larsson, 1954; Doty-'-
~
al., 1959;
Sprague !! al., 1961; Skultety!! al., 1962; Erlich
and Glickman, 1966; Routtenberg and Kane, 1966; Wyrwicka
and Dot Y, 1966);
Subcortical structures in the forebrain are also
involved in feeding.
For example, hyperphagia resulting
fram ventramedial hypothalamic lesions is increased by
les ions of the amygdala (Anamd and Brobeck, 1952; Morgane
and Kosman, 1959, 1960).
Moreover, stimulation of the
amygdala disrupts eating, at least during the period of
stimulation (Shealy and Peele, 1957; Fonberg and Delgado,
1957).
These data, taken together, show that many areas
of the brain are involved in hunger motivation or
consummatory regulation.
Many investigators in the
field have stressed the importance of viewing the control
- 6 of food intake as the resu1t of activity in severa1
cortical, 1imbic-rhinencepha1ic, and brainstem areas,
as we11 as in the various periphera1 afferent systems
interacting with hypotha1amic structures in the intact,
normal organism (Ste11ar, 1954; MBcKay, 1959; Morgane,
1962; Rob i.ns on , 1964).
Neverthe1ess, interest has
centered on the hypothalamus as the essentia1 structure
invo1ved in regu1ation, since it is anatomica11y 1inked
direct1y and extensive1y with a11 of the neural systems
mentioned above (Stevenson and Rixon, 1957) and is known
to be a major intergrative center for a variety of
homeostatic functions (Ste11ar, 1954).
Hypothalamus
Considerable evidence concerning the functions of
hypotha1amic areas in the regu1ation of food intake has
been obtained in the years since stereotaxie techniques
became avai1ab1e.
Most of the research done on hypotha1amic
mechanisms has invo1ved e1ectro1ytic les ions of discrete
areas in order to identify the structures which are
necessary for maintenance of normal food intake and to
determine how these structures interact.
The ventromedia1
nucleus was first identified as important for the control
- 7 -
of feeding by Hetherington and Ranson (1942; He theringt on ,
1941).
da~ge
Further investigation revea1ed that bi1atera1
to the ventromedia1 nucleus produces hyperphagia
and obesity whi1e damage to portions of the 1atera1 nucleus
resu1ts in aphagia (Brobeck et al., 1943; Brobeck, 1946;
Anand and Brobeck, 1951a,b).
These observations are
supported by experiments using e1ectrica1 and chemica1
stimulation techniques.
E1ectrica1 stimulation of the
1atera1 hypothalamus has been shown to cause "stimu1usbound" feeding (Smith, 1956; Miller, 1957, 1960; Morgane,
1961) as we11 as a post-stimulation increase in food
intake (Delgado and Anand, 1953; Anand and Dua, 1955).
In contrast, stimu1a"tion of the ventromedia1 area
disrupts ongoing feeding (Anand and Dua, 1955; Kra sne ,
1962; Oomura et al., 1967).
Chemica1 stimulation of
these areas has further supported the notion of a
reciproca1 relation between the ventromedia1 and 1atera1
regions.
Grossman (1960, 1962a,b) and Miller (1965)
e1icited eating in satiated rats by injecting adrenergic
substances into the 1atera1 hypothalamus.
Injections
of hypertonic saline into the 1atera1 hypothalamus a1so
produce eating (Epstein, 1960), and a decrease in
consumption resu1ts from simi1ar stimulation of the
- 8 -
ventromedia1 hypothalamus.
Procaine-HC1, a depressant,
has opposite effects in both areas.
A1though it is recognized that the regu1ation of
food intake is not exc1usively hypotha1amic, two major
theories concerning the ro1e of hypotha1amic nuc1ei in
regu1ation have been proposed.
Brobeck (1955, 1957;
Strominger and Brobeck, 1953) deve10ped a mu1ti-factor,
thermoregu1atory theory of food intake.
In Brobeck's
view, the organism's energy balance is main1y dependent
upon temperature regu1ation, which in turn is contro11ed
by food intake. Periphera1 mechanisms are invoked to
account for short-term changes in feeding behavior, but
the major contro11ing factors in Brobeck's theory are
body temperature, environmenta1 temperature, and changes
in the organism's metabo1ic rate (heat production) after
food ingestion.
Brobeck proposes that the increase in
heat production in the organism some after eating causes
anincrease in body and brain temperatures which affects
thermoreceptors in the preoptic region of the hypothalamus.
These thermoreceptors, in turn, inhibit further eating,
perhaps by inf1uencing the activity of the latera1 and
ventromedia1 hypothalamus (Andersson and Larsson, 1961).
An alternative theory, invo1ving ventromedia1 hypo-
- 9 tha1amic glucoreceptors, has been proposed by Mayer (1953,
1955; Mayer and Thomas, 1967).
The contro11ing factor in
Mayer's theory of regu1ation is carbohydrate metabo1ism,
and since glucose uti1ization contro1s, in turn, the
metabo1ism of fat and protein, the hypothetica1 "glucostatic"
mechanism cou1d regu1ate the organism's energy metabo1ism
in genera1.
Periphera1 factors such as gastric gluco-
receptors and oropharyngea1 stimulation cou1d contribute
to shart-term control of feeding whi1e 10ng-term bodyweight maintenance might depend on changes in 1ipid
metabo1ism.
The integration of a11 these mechanisms,
however, is accomp1ished through the "glucostatic"
regu1atory system in the hypothalamus.
The ventromedia1
glucoreceptors are he1d to be sensitive to the rate of
glucose uti1ization by the organism, and the activity of
these glucoreceptors inhibits the 1atera1 hypotha1amic
mechanisms which initiate feeding.
Evidence has been gathered to support both Mayer's
and Brobeck's hypotheses, and in fact neither position
necessari1y exc1udes the other.
Both regu1atory systems
may be viewed as different, interdependent aspects of a
comp1ex mechanism governing the organism's genera1
energy balance.
The "glucostat" cou1d be inc1uded in
- 10 Brobeck's multi-factor theory, since thermoregulation
may involve glucose utilization at some stage (Brobeck,
1957).
Electrophysiological Studies
Electrophysiological studies concerning the effects
of blood glucose levels on hypothalamic activity have
sampled single units or observed changes in electroencephalographic (EEG) activity.
Anand et al. (1962,
1964) have recorded increased activity in ventromedial
units in anesthetized cats and dogs during increased
glucose utilization measured by arteriovenous glucose
differences.
They also found a decrease in ventromedial
cell activity during hypoglycemia.
Activity in lateral
hypothalamic cells varied reciprocally with activity in
the ventromedial cells.
These effects were independent
of the osmolarity of the injected glucose and were
observed to vary with the magnitude of arteriovenous
glucose differences rather than with blood glucose level
alone.
Similarly, Oomura et al. (1964, 1967) noted
ventromedial unit activity increases and lateral unit
decreases in response to glucose injections, and again
the effects were seen to be independent of the hypertonicity
- 11 of injected substances.
They a1so recorded decreases in
1atera1 hypotha1amic unit activity in cats during and
~ediate1y
after e1ectrica1 stimulation of the ventro-
media1 area and a corresponding decrease in ventromedia1
ce11 firing rates during stimulation of the 1atera1
hypothalamus.
Differences in EEG activity between the 1atera1 and
ventromedia1 areas have a1so been observed.
Sharma et al.
(1961) recorded EEG in both areas or cats and monkeys
during stomach distension and found an increase in the
amplitude of irregu1ar waves in the ventromedia1 nucleus
but no change in 1atera1 nucleus activity.
They a1so
observed that intravenous injections of glucagon (which
raises the b100d glucose 1eve1 and increases glucose
uti1ization) produces an increase in ventromedia1 EEG
amplitude and a decrease in its frequency, again with
no change in the EEG of the 1atera1 area.
Simi1ar
observations were made by Anand et al. (1961), who
recorded increases in EEG frequency without amplitude
changes in the ventromedia1 area fo110wing intravenous
injections of glucose in monkeys.
A decrease in EEG
amplitude without a change in frequency was seen in
- 12 the lateral hypothalamus.
In contrast, insulin produced
a decrease in the frequency and an increase in the amplitude
of the ventromedial EEG and a slight increase in the
frequency of the lateral hypothalamic EEG. Oomura et al.
(1967), working with chronically prepared cats, report
EEG synchronization in the lateral hypothalamus and desynchronization in the ventromedial nucleus during eating.
These studies lend support to the notion that
reciprocal interactions of the lateral and ventromedial
hypothalamic nuclei are directly involved in the regulation
of food intake, and that glucose is at least one of the
factors controlling this mechanism.
There are, however,
serious difficulties in the interpretation of EEG and
unit data.
Little is known about the nature of the
neurophysiological events underlying the EEG, and a
single EEG pattern may be associated with a variety of
experimental effects (Morre Il , 1961).
Moreover, single-
unit studies indicate that the relation between the form
and amplitude of EEG waves and the discharge rates of
ne~ons
at the same recording site is a complex one
(Cross and Silver, 1966; Morrell, 1967; Creutzfeld
1966).
~
Furthermore, EEG recording does not provide
al.,
- 13 reliab1e information about activity 1eve1s in d.iscrete,
localized brain areas, as indicated by multi-unit
recordings (Buchwa1d
~
al., 1966; Bambridge, 1968).
Individua1 unit data is better understood, but practical
considerations limit the number of cells sampled in a
given area.
Furthermore, it is difficult to make
genera1izations about an entire brain arèa on the basis
of a few dubiously representative components.
Multiple-unit (flmu1ti-unit fl ) activity recording
has been shown to be a more reliable and sensitive
method of observing neural activity than the EEG technique
(Bambridge, 1968).
On
the other hand, it integrates or
flsummarizes" the activity of a population of ce11s at
the recording site and therefore provides a more
representative picture of neural activity in the area
under investigation than does the single-ce1l approach.
Since theories of hypotha1amic regulatory function are
based on activity 1evels of ce11 populations, the mu1tiunit technique seems most appropriate for obtaining
information relevant to those theories.
The purpose of this study was to observe changes in
multi-unit activity in the lateral, ventromedial, and
- 14 other hypotha1amic areas fo110wing intravenous injections
of glucose and insu1in and during mechanica1 distension
of the stomach.
Such observations might provide a
clearer view of the responses of these areas and how
they interact than has been obtained so far with other
recording techniques.
METHODS
Subjects
The subjects were 20 male adu1t mongre1 cats
weighing 1.5 to 4.0 ki10grams.
Procedure
Each subject was depnived of food (but not water)
for 20-24 hrs. before an experiment and was anesthetized
with sodium pentotho1 (1.8 mg/kg) intraperitoneal1y (IP)
fo1lowed by 12.5% or 25% urethane in disti11ed water
intravenous1y (IV) as needed, or with sodium pentobarbito1
(35 mg/kg) IP, with supp1ementary doses given IV as needed.
The Snider and Niemer (1961) stereotaxie atlas of the eat
brain was used to position e1ectrodes in the desired
hypothalamic areas.
Monopo1ar and bipo1ar e1ectrodes were used.
Monopo1ar
- 15 electrodes were constructed of 250u stainless steel wire
etched to a conical point and coated with insulating
compound No. 741 (National Engineering Products, Inc.)
to within about
~
mm. of the tip.
electrodes ranged from 10 to 30 K.
Impedances of these
Reference electrodes
consisted of short lengths of bar stainless stell wire
inserted into the frontal sinus through a hold drilled
in the top of the skull.
Bipolar electrodes were made
of two 250u formvar-insulated wires twisted together,
with the bare tips separated by approximately 1 mm.
SignaIs were led from the cat through a cable made
up of eight Microdot low noise cables (#250-3804) and,
via selector switches, to (a) a-c channels of a Grass
model 7 polygraph for electroencephalographic (EEG)
recording and (b) the high-frequency recording equipment.
A block diagram of the electrical recording system is
shown in Figure 1.
High-frequency signaIs were first
amplified by Tektronix DifferentiaI Amplifiers (type
2A6l).
The pass band (using the built-in filters) was
set at 600Hz to 6,000Hz (half-amplitude, -20db/decade).
The 600Hz setting permits transmission of signaIs within
the action potential frequency range but blocks EEG and
- 16 . other slow electrical activity.
The upper cut-off reduces
the possibility of contamination from extraneous radio
frequency signaIs.
The amplified signaIs were then led
to audio and CRT monitors and were averaged by integrating
circuits (see Figure 2) modified from Weber and Buchwald
(1965).
The d-c output of this circuit is proportional
to the root-mean-square of a 1,OOOHz sine wave input,
and its time constant is about 800 msec.
The integrator
outputs from two electrodes were recorded on the d-c
channels of the polygraph simultaneously with the EEG
records from the same electrodes, as weIl as on a Leeds
and Northrup Speedomax Xl-X2 two-channel servo-recorder
with a chart speed of
~inch/min.
The polygraph chart
permitted comparisons of details in simultaneous EEG and
multi-unit activity levels.
The servo-recorder provided
a convenient display of slower changes in multi-unit
activity.
The noise level of the system, within the pass band
used, was determined by measuring the d-c output of the
integrator with the electrodes still in the brain of the
sacrificed cat.
SignaIs exceed noise levels by 2/1 to 15/1.
2% changes in the d-c output were discriminable even at low
- 17 signal 1eve1s.
The peak-to-peak range of input signal
1eve1s on the scope face was about 10 to 30 uv.
Discrete injections of glucose (of varying
concentration in saline) or insu1in (20 to 60 units,
made from zinc-insu1in 'crystal) were administered
through a short 1ength of PE 50 cannu1a tubing inserted
into the femora1 veine
A one-way stopcock (B-D
MS-10)
with two in1ets connected syringes to the cannu1a.
In
a11 cases, injection of glucose, insu1in, or anesthetic
was fo110wed immediate1y with sufficient 0.9% saline to
c1ear the cannu1a tube.
Injections were made at a rate
of 2.5 to 5 cc. per minute.
Pro10nged administration of 10% glucose-saline was
accomp1ished by dripping the solution at a rate of
approximate1y 1 cc. per minute through a 25 guage need1e
inserted in the femora1 veine
Control infusions of
isosmotic or hyperosmotic saline were administered in
the same way.
In 2 subjects, the stomach was distended by inserting
a condom, fixed to the end of a three foot 1ength of
PE 150 tubing, through the mouth into the stomach. Water
was pumped into the condom from a 30cc. syringe.
- 18 Histology
At the conclusion of each experiment, a 1 mA, d-c
current was passed through the electrodes for 15-20 seconds,
after which the brain was blocked at the same angle as
the electrode penetrations while the subject was still
fixed in the stereotaxic instrument.
Then the block was
removed and placed in formol-saline solution containing
about 2% potassium ferricyanide.
SOu or 75u sections
were sliced from the frozen block, mounted on slides,
and stained with neutral red.
In a few subjects, no
current was passed through the electrodes, and slices
were stained with cresyl violet.
8" by 10" photographic enlargements were made
directly from the covered slides to facilitate
identification of recording sites.
Slides were placed
into the negative holder of a standard enlarger with
the lens opening set at fll, and the focussed image
of the stained section was projected onto high contrast
~
(f5) glossy photographic paper, which was then developed
in Dektol.
- 19 RESULTS
Activity Leve1s
Most studies of unit activity in the hypothalamus
revea1 re1ative1y 10w tonic firing rates, even in
unanesthetized, immobi1ized preparations (Cross and
Si1ver, 1966; Lincoln, 1966).
Consequent1y, many
investigators of hypotha1amic neural activity have
emp10yed muscle relaxants cambined with local anesthetics,
or genera1 anesthetics such as urethane which are thought
to have a minimal effect on the hypothalamus.
According1y,
the use of urethane in this study was intended to obviate
the severe depression of hypotha1amic activity
encountered with barbituate anesthesia (Brooks, 1959;
Stuart et al., 1964).
Camparisons of records obtained
in this study from subjects anesthetized with nembuta1
and with urethane indicate that nembuta1 does have the
more pronounced depressive effect on hypotha1amic mu1tiunit activity
in the cat.
A1though responses to
experimenta1 treatments were obtained using either type
of anesthetic, those recorded under urethane were
genera11y more marked.
Mu1ti-unit activity 1eve1s in the 1atera1 hypothalamus
- 20 -
(LH), mammi11ary nuc1ei, and posterior hypotha1amic area
were genera11y higher, by a factor of three or four, than
those recorded from the ventromedia1 (VMH) and anterior
hypotha1amic areas.
Base-1ine, 1 to 2 sec. fluctuations
of the LH mu1ti-unit records were more pronounced than
those of the VMH (Figure 4).
Very sma11 shifts in e1ectrode position within the
hypothalamus often produced appreciab1e changes in
recorded activity 1eve1s, suggesting that re1ative1y
discrete portions of the anatomica1 loci under
investigation dominated the records obtained in this
study (Figure S a, b, c, d).
This agrees with the
findings of Halas and Beardsley (1968) concerning the
loca1ization of mu1ti-unit recording in sensory nuc1ei.
Glucose Injection Effects
Mu1ti-unit and EEG responses to glucose injections
and infusions are summarized in Figure 3.
Injections
of Sec. of 30% glucose solutions in disti11ed water
resu1ted in decreases of mu1ti-unit activity in the LH.
These decreases were sometimes transient, lasting five
to fifteen minutes, but were more often prolonged,
- 21 showing 1itt1e or no recovery throughout the recording
session (Figure
6~,
b).
Differences in the duration of this effect might
be due to variation in the amounts of previous1y
injected glucose, rates of glucose uti1ization, the
deprivation states of the subjects, or the positions
of the e1ectrodes within the LH.
Simi1ar decreases in
mu1ti-unit activity were recorded from the 1atera1
mammi11ary nucleus (Figure 6c) and the posterior
hypotha1amic area (Figure 6d).
Injections of Sec.
of isotonie or 25% saline either increased mu1ti-unit
activity or had no effect in these areas.
Increased mu1ti-unit activity in response to
glucose was recorded from the VMH (Figure 7b, d).
Saline injections did not change activity 1eve1s in
this area.
Neither glucose nor saline affected mu1ti-
unit activity 1eve1s in the media1 mammil1ary nucleus
or the supramammi11ary decussation (Figure 8a, b).
The amplitudes of EEG records taken from the
various recording sites, or from the same site in
different subjects, varied with the type of e1ectrode
used and with the tip separations of different bipo1ar
- 22 -
e1ectrodes.
Cross-comparison
of base1ine EEG records
from the areas under investigation was therefore not
possible a10ng this parameter.
Slight changes in EEG
frequency or amplitude, however, did occur in some cases
in response to glucose injections within a session at a
given recording site.
Injections of Scc. of 30% glucose produced a slight
increase in the amplitude of the EEG in the LH without
a noticeab1e change in frequency (Figure 9a).
The
amplitude of the VMH EEG decreased in response to
glucose injections (Figure 9b).
These changes occurred
within 10 minutes after the injections and genera11y
fo110wed the time courses of simu1taneous1y changing
mu1ti-unit records.
No effects of glucose on EEG
patterns were noted in the mammi11ary nuc1ei (Figure
9d, e).
Glucose Infusion Effects
Infusion of 10% glucose-saline resu1ted in gradual
decreases in mu1ti-unit activity of the LH, zona incerta,
posterior hypothalamus, and the 1atera1 mammi1lary
nucleus (Figure 10a, b, c, d).
No changes in activity
1eve1s were seen in the medial mammi11ary nucleus, the
- 23 ventral posteromedial nucleus, or the anterior
hypothalamic area.
Increased activity during glucose
infusion was recorded from the VMH (Figure lIa) and
the fields of Forel--prerubral field (Figure lIb).
Control infusions of 0.9%, 5%, and 10% saline did
not change acitivity levels at any recording site,
except in two cases where 10% saline produced slight
increases in activity in the fields of Forel--prerubral
field and in the ventral posteromedial nucleus.
Saline
infusion following glucose infusion halted activity level
changes due to glucose about half the time.
Otherwise,
the saline had little effect on the records--ongoing
decreases or increases contlnued during saline infusion,
diminishing on1y after 20 to 40 minutes of saline
infusion, if atall.
This persistence of the glucose
effect was observed at most recording sites and wifu
aIl concentrations of infused saline.
In addition to long-term activity changes, some
short-term changes in the multi-unit records were
occasionally seen with electrode placements in the LH
and posterior hypothalamic area.
These changes took
the form of peaked bursts or drops in activity, were
- 24 -
of approximately 0.5 to 3 minute's duration, and
occurred with increasing magnitude and frequency
during glucose infusion.
Saline infusion d,iminished
or terminated the effect (Figure 12).
The EEG activity of some areas was also affected,
but not reliably, by glucose infusion.
The most marked
changes were seen in the posterior hypothalamus of one
subject, where glucose infusion synchronized the EEG
(Figure 13) while th e mu1ti-unit acmrity level was
falling.
Saline infusion diminished the multi-unit
activity changes and reduced the amplitude of the EEG.
In most cases, however, EEG changes were slight and
difficult to observe by simple inspection of the records.
Filtering out a11 but 1-15Hz activity did not seem to
change the response of the EEG to glucose.
The amplitude
of the VMH EEG was increased. with glucose infusion in
one case (Figure l4a) but was decreased in two other
subjects (Figure l4b, c).
LH EEG activity changes were
a1so inconsistent, none occurring in three cases (Figure
l4d, e, f) but a slight increase in frequency being
visible in one record (Figure l4g).
Increases in both
frequency and amplitude of EEG records fram the fields
- 25 of Forel--prerubral field and from the ventral
posteromedial nucleus were observed during glucose
infusion (Fig. 15a, b).
A slight decrease in EEG
frequency was recorded from the anterior hypotha1amic
area in one subject (Fig. 15c).
Insu1in Effects
Fort y to sixt Y minutes were a110wed for the insu1in
to exert its effect on the hypothalamus.
Changes in
mu1ti-unit activity fo11owing injections of 40 to 80
units of insu1in were very sma11 and unre1iab1e in the
zona incerta and 1atera1 mammi11ary nucleus.
No changes
in response to insu1in injections were observed in the
LH, VMH, media1 mammi11ary nucleus, or anferior
hypotha1amic area.
In sorne cases, EEG pattern changes
occurred within the observation periode
Slight
amplitude increases in the LH and amplitude decreases
in the 1atera1 mammi11ary nucleus were noted, but in
genera1 the EEG was as unresponsive to insu1in as was
the mu1ti-unit activity.
A1though the type of insu1in
used in this study does not exert a maximum effect
unti1 three to six hours after injection, it does begin
- 26 removing glucose from the blood within approximately
thirty minutes.
A longer observation period may be
required, however, before changes in multi-unit
activity become noticeable.
Stomach Distension Effects
Distension of the stomach produced only slight
increases in multi-unit activity levels in the posterior
hypothalamic area, the LH, the zona incerta, and the
interpeduncular nucleus.
These changes were abrupt
and were se en only intermittently during maximum
distension.
They appeared to be related to arousal
phenomena, since they resembled activity increases
seen at other times in lightly anesthetized preparations
undergoing painful stimulation.
No changes were apparent in the EEG records during
or after stomach distension in any of the preparations.
Supplementary Observations
The effects of additional small doses of anesthetic
required occassionally for maintaining anesthesia
differed in severity with the type of anesthetic employed.
In the lightly anesthetized subject, nembutal caused
- 27 -
multi-unit activity to fall sharply and to remain
depressed for relatively long periods of time.
Comparable
supplementary doses of urethane, on the other hand,
depressed activity less markedly and for much shorter
periods of
t~e.
Although the effects of such doses
of urethane were transient in the hypothalamus, general
anesthesia of the subject was augmented sufficiently
even after the hypothalamic activity recovered, suggesting
that urethane acts selectively on extra-hypothalamic
structures.
barbituate
Urethane therefore seems preferable to
anesthesia in studies concerning hypothalamic
neural activity.
In order to facilitate accurate electrode placements,
multi-unit activity patterns were observed at several levels
as electrodes were lowered in stages to intended recording
sites.
It was hoped that characteristic activity patterns
could be discerned in at least some of the areas under
investigation.
This proved not to be the case in aIl
but the posterior hypothalamic area.
As the electrode
passed through this area, an easily identifiable
"bursting" pattern was seen on the multi-unit recording
chart (Figure Sb, d).
This pattern was useful, not only
- 28 for identifying the posterior hypothalamic area, but
also for placing electrodes in adjacent areas such as
the mammillary nuclei.
from about
~1.6
The "bursting" area extended
mm vertically to
~2.5
mm and from 7.5
to 8.5 anterior to zero in the atlas used, probably
encompassing the entire posterior hypothalamic area.
Perhaps a more thorough survey of the hypothalamus
wou Id reveal other structures with characteristic
multi-unit activity patterns.
Such patterns could
facilitate electrode orientation in or near the
structures which generate them and might weIl be worth
investigating in themselves.
DISCUSSION
The results of this study support the concept that
changes in blood glucose level or glucose utilization
influence the activity of hypothalamic structures known
to be intimately involved in the regulation of food
intake.
Although it is difficult to estimate the ways
in which the types and amounts of anesthetics used here
distort normal hypothalamic activity patterns, the
similarity of data obtained under two different
anesthetics encourages confidence in these results.
- 29 Changes in mu1ti-unit activity in the LH and VMH were
re1iab1e and in the expected directions.
Moreover,
there is essentia1 agreement between the resu1ts of
glucose injections and glucose infusions in the areas
investigated under both treatments.
Insufficient
observations were made with simu1taneous LH and VMH
e1ectrode placements to warrant any firm statement
about the relations of activity changes between the
two areas, but the data indicate that the structures
do function reciproca11y and that glucose p1ays an
important part, direct1y or indirect1y, in a1tering
their activity.
The rapid onset of the glucose effect in both LH
and VMH fo11owing injections suggests either that glucose
acts direct1y on both areas or that it acts on one of
the structures, which has relative1y direct connections
with the other.
Oomura
~
al. (1967) have noted that
e1ectrical stimulation of either
area inhibits unit
activity in the other for severa1 seconds after stimulation
is terminated.
Collateral anatomica1 connections in both
directions between the LH and VMH have been demonstrated
(Szentagothai et al., 1962), and these pathways may
- 30 -
mediate reciproca1 interactions between the areas.
Oomura et al. point out that differences in chemica1
transmitter metabo1ism in the LH and VMH cou1d account
for the observed slow ttme-course of inhibition in one
area with excitation in the other in the absence of
internuncia1 processes between them.
Thus, excitation
of one area cou1d be conducted through collateral
processes to the other area, causing inhibition of
activity in the latter structure by virtue of differences"
in receptor site properties of the two areas.
Oomura et al. (1967) and others (Sawa
~
al., 1959;
Tsubokawa and Sutin, 1963), have a1so found evidence of
reciproca1 LH and VMH interactions with the 1imbic system,
amygda1a, septum,
portions of the globus pa11idus, and
the mesencepha1ic tegmentum.
Such interaction cou1d
play a part in LH-VMH relations and in the
observed
persistence of reciprocal effects in these areas.
The
diversity of hypotha1amic structures affected by glucose
observed in this study indicates that these and probab1y
other portions of the hypothalamus may a1so participate
in LH-VMH interadions.
Both the thermoregu1atory and
the glucostatic theories of regulation tend to invo1ve
- 31 on1y a sma11 number of hypotha1amic structures in
their mechanisms.
The data of this study suggest
that such a view of hypotha1amic participation in
regu1ation may be too ltmited.
The full significance
of EEG and mu1ti-unit activity 1eve1 changes observed
in hypotha1amic areas other than the LH and VMH is
difficu1t,to assess without a more complete survey of
the hypothalamus.
Some of the long-term changes recorded during
glucose infusions may be re1ated to changes in depth
of anesthesia.
This is a particu1arly importRnt
consideration in the case of anterior hypotha1amic
or mammil1ary nuc1eus.p1acements.
These areas
hav~
been imp1icated in the regulation of sleeping and
waking (Rans on , 1939; Nauta, 1946), the anterior
hypotha1amic area being termed a "sleeping center"
and the region of the mammil1ary nuc1ei termed a
"waking center".
Thus, it is possible that changes
in multi-unit activity levels observed in these
structures were associated more direct1y with the
anesthetic state of the preparation than with b100d
glucose level or glucose metabo1ism. If that is the
- 32 case, however, it remains a problem to explain why
the observed changes correlate so closely with changes
in the infused substances, and why transient shifts
in activity levels were recorded in these areas in
response to discrete glucose injections.
Similar
considerations apply in the other hypothalamic areas
examined here.
Responses in the fields of Forel--
prerubral field, posterior hypothalamus, and ventral
posteromedial nucleus were not expected t yet they are
clearly associated with the experimental treatments.
Factors such as temperature and pH of injected substances,
hypervolemia, etc., were not rigidly controlled, and
these variables must be eliminated by further experimentation before the observed responses can be definitely
attributed to glucose.
The results of this study, taken together, agree
with the data of lesion studies and electrical stimulation
experiments described in the introduction.
More definite
statements concerning normal LH-VMH multi-unit activity
relationships and interactions with other hypothalamie
areas can be made with
~idence
only in the light of
records obtained from chronic preparations and from
- 33 -
studies exp1icit1y concerned with the detai1ed nature
of interactions between these areas.
More extensive
recording throughout the hypothalamus, particu1ar1y in
the preoptic areas and the amygda1a, will a1so he1p to
c1arify the picture of hypotha1amic glucose effects.
The data of these experiments tend to favor Mayer's
interpretation of food intake regu1ation, since LH
activity was never seen to increase, nor VMH activity
to decrease, when the body (and presumab1y b100d)
temperature of a preparation was fa11ing under anesthesia.
It is possible that separate mechanisms operate in the
normal animal, with preoptic thermoregu1ation affecting
food intake through structures "downstream" from the LH
and VMH.
The resu1ts of this study, however, do not
support the notion that changes in the preoptic areas
in response to body temperature changes influence either
the LH or the VMH.
The short 1atency of the glucose effect indicates
that the influence of glucose on hypotha1amic regu1atory
centers is 1imited in time on1y by the rate of absorption
of glucose into the b100dstream.
As suggested by both
Mayer and Brobeck, periphera1 stimuli associated with
- 34 -
conS:Uinmatory behavior may weIl limit the amount of
food ingested or the duration of consummatory behavior
in a feeding episode prior to absorption, but glucose
metabolism could de termine the lengths of intervals
between occurrences of appetitive behavior.
The action
of glucose on the hypothalamus is at least rapid enough
to control post-ingestion satiety and subsequent "hunger".
Inconsistencies between EEG and multi-unit activity
effects are not surprising, sinee the two measures concern
different neural phenomena.
Ideally, the EEG might be
used to distinguish multi-unit activity changes due to
altered firing patterns in fibers synapsing at the
recording site fram changes due to altered firing rates
in fibers passing through the recording site, but no
such distinctions could be made in these experiments.
At a given site in a particular preparation, EEG
changes and multi-unit changes did not consistently
aecompany each other.
In general, the EEG remained
less sensitive to experimental treatments than did
multi-unit activity levels.
The apparent ubiquity of glucose effects in the
hypothalamus trnmediately raises questions about the
- 35 nature of interactions between the areas involved.
Further studies should be undertaken to investigate
functional relations between specifie hypothalamie
l~ci
in order to determine whether changes in a given
structure are induced directly by glucose or other
substances, or by the activity of other anatomically
connected structures.
A procedure combining localized
chemical sttmulation and multi-unit recording techniques
could be useful in this endeavor.
Correlations between
normal behavior, chemically induced behavior, and
simultaneous multi-unit activity recorded under both
conditions in various hypothalamic loci could help
ascertain the relations among different areas.
If
regulatory functions of the hypothalamus are indeed
based upon relative levels of tonie activity in
hypothalamic areas, the multi-unit recording technique
would be particularly appropriate for detailed
investigation of these functions.
SUMMARY
Multiple unit activity was seen to decrease in the
lateraI hypothalamus, zona incerta, lateral mammillary
- 36 nucleus, and the posterior hypotha1amic area fo110wing
injections of 30% glucose and during infusions of 10%
glucose.
Increases of activity were observed in the
ventromedia1 hypothalamus and the fields of Fore1-prerubra1 field area under simi1ar conditiQns.
No
changes in activity 1eve1s were observed in the media1
mammi11ary nucleus, the anterior hypothalamus, or the
ventral posteromedia1 nucleus.
EEG effects in these
areas were in some cases unre1iab1e or inconsistent,
and the EEG was found to be general1y not as responsive
as mu1ti-unit activity to glucose treatment.
Urethane
was seen to be preferable to barbituate anesthetics
for hypotha1amic recording studies of this nature.
Sorne
indication of the size of the area of tissue generating
the mu1ti-unit records was provided by changes in the
1evel and form of the records as e1ectrodes were shifted
in small steps through the hypothalamus.
Distension of
the stomach produced only arousal-re1ated, abrupt
increases in activity 1evels in the posterior and
lateral hypothalamic areas and the zona incerta.
Insulin
injections had litt1e effect on activity levels in the
1ateral, ventromedial, or anterior hypothalamic areas
- 37 -
or in the medial mammillary nucleus.
The data indicate
that glucose in the blood has rapid, widespread, and
reciprocal effects in the hypothalamus, and that
hypothalamic participation in food intake regulation
very likely involves more than a simple, two-structure
mechanism.
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R., Yamamoto, T., and Naka, F.
Recip-
roca1 re1ationship of the 1atera1 and ventromedia1
hypothalamus in the regu1ation of food intake.
io10gy and Behavior, 1967,
Pfaffman, C.
~,
Phys-
97-115.
The p1easures of sensation.
Psycho10gica1
Review, 1960, 67, 253-268.
Pribram, K.R., and Bagshaw, M.
Further ana1ysis of the
temporal lobe syndrome uti1izing front-temporal ablations.
Journal of comparative Neuro10gy, 1953, 99,
347-375.
Rans on , S.W.
Somnolence caused by hypothalamic 1esions in
the monkey.
Archives of Neuro10gy and Psychiatry,
1939, 41, 1-23.
Richter, C.P., and Hawkes, C.D.
Increased spontaneous act-
ivity and food intake produced in rats by remova1 of
the frontal po1es of the brain.
and Psychiatry, 1939,
Robinson, B.W.
~,
Journal of Neuro10gy
231-242.
Forebrain alimentary responses: some org-
anizationa1 princip1es.
In: Thirst, first interna-
tional symposium on thirst in the regu1ation of body
water. New York:Pergamon Press, 1964.
- 49 Routtenberg, A., and Kane, R.S.
Weight 108s following les-
ions at the self-stimulation point: ventral midbrain
tegmentum.
Canadian Journal of Psxchology, 1966, 20
(4), 343-351.
Sawa, M., Maruyama, N., Hanai, T., and Kaji, S.
Regula tory
influence of amygdaloid nuclei upon the unitary activity in ventr6medial nucleus of hypothalamus.
psychiat. neurol. jap., 1959, 13, 235-256.
Folia
Cited by
Oomura et al., 1967.
Share, l., Martyniuk, E., and Grossman, M. l.
Effect of pro-
longed intragastric feeding on oral food intake in
dogs.
American Journal of PhxsiologX, 1952, 169,
229-235.
Sharma, K.N., Anand, B.K., Dua, S., and Singh, B.
Role of
stomach in regulation of activities of hypothalamic
feeding centers.
American Journal of Physiology,
1961, 201, 593-598.
Shealy, C.N., and Peele, T.L.
of cat.
Studies on amygdoid nucleus
Journal of Neurophysiology, 1957, 20, 125-139.
Sherrington, C.S.
In: Textbook of phxsiology. Vol. 2.
Scheaffer, E.A. (Ed.), Edinburgh: Pentland, 1900. P.920.
- 50 Skultety, F.M.
Changes in calorie intake fo110wing brain
stem lesions in cats. III. Effects of lesions of the
periaquaducta1 gray matter and rostral hypothalamus.
Archives of Neurology, 1966, 14, 670-680.
Smith, D.A.
Stimulation of latera1 and media1 hypothalamus
and food intake in the rat.
Anatomical Record, 1956,
124, 363-364.
Snider, R.S., and Niemer, W.T.
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A stereotaxie atlas of the
Chicago: University of Chicago Press,
1961.
Sprague, J.M., Chambers, W.W., and Stel1ar, E.
affective, and
a~aptive
Attentive,
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Science,
1961, 133, 165-173.
Ste1lar, E.
The physiology of motivation.
Psycho10gica1
Review, 1954, 61(1), 5-22.
Stevenson, J.A.F., and Rixon, R.H.
Environmenta1 temper-
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Yale Journal of Biology
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Strominger, J.L., and Brobeck, J.R.
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A mechanism of regu-
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Hypothalamic unit activity. l. Visceral and somatic
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Electroencephalography and clinical Neur-
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Szentagothai, J., Flerko, B., Mess, B., and Halase, B.
Hypothalmic control of the anterior pituitary. Budapest: Akadamiai Kiado, 1962.
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1967.
Teitelbaum, p., and Epstein, A.N.
The role of taste and
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Teitelbaum, p.
London: Pergamon Press, 1963.
The biology of drive.
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Tsang, Y.C.
pp.
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Hunger motivation in gastrectomized rats.
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Tsubokawa, T., and Sutin, J.
Mesencephalic influence upon
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Hunger sensations in
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Watts, J.W., and Fulton, J.F.
Intussusception--the relation
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Weber, D.S., and Buchwald, J.S.
A technique for recording
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E1ectroencepha1o-
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Woods, J.W.
Behavior of chronic decerebrate rats.
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Journal
- 53 -
2A6l,
Amplifiers
and
Filters
Integrators
Electrode
Selector
Switches
Monitor
(see Figure 2)
Cat
Dual Channe 1
Servo-recorder
(integrated
units)
Polygraph
(EEG, integrated
units)
Figure 1.
Block dia gram of electrical recording system.
- 54 -
Output to
Servo-recorder &
Polygraph
Output
Bias
Circuit
. 5.2K
6K
50uf
l6.5K
60Hz
O.02uf
Multi-unit
Input fram
Amplifier
Figure 2.
Integrator circuit.
e
e
GLUCOSE INFUSIONS
GLUCOSE INJECTIONS
ELECTRODE PLACEMENTS
MULTI-UNIT
ACTIVITY
Lateral Hypothalamus
decreases
Ventromedial hypothalamus
increases
EEG
increased
amplitude
decreased
amplitude
-
MULTI-UNIT
ACTIVITY
EEG
decreases
increased freq.
or
no change
increases
inconsistent
no change
no change
no change
no change
Lateral mammillary nucleus
decreases
no change
decreases
no change
Posterior hypothalamic area
decreases
no change
decreases
increased
amplitude
Supramammillary decussation
no change
no change
Medial mammillary nucleus
Anterior hypothalamic area
no change
no change
Zona incerta
decreases
no change
Fields of Forel/prerubral
increases
increased
amp. & freq.
Ventral posteromedial nuc.
no change
increased
amplitude
Figure 3. Table summarizing glucose injection and infusion effects on EEG and
multi-unit activity.
r
Ut
Ut
Figure 4a.
Upper trace: typical multi-unit activity
record fram the ventramedial hypothalamus
at slow chart speed, showing relatively
low activity level and small, 1-5 second
fluctuations in activity.
Lower trace:
fast chart speed record from portion of
upper record, showing fluctuations more
clearly.
Figure 4b.
Upper trace: typical, high multi-unit
,,"
.....
.....
,
~
acitivty level/recorded from the lateral
",·,1
•.• 'o'-
hypothalamus, with larger (although
approximately proportional) short-term
activity fluctuations than cammonly
found in the ventromedial area.
Lower
trace: fast chart speed record showing
details of activity fluètuations.
- 56 -
------------------------------..r--___
10% 1
...__
1 sée.
Figure 4a.
-------------....-----------------------------------_._10%1.._ _
1 sec.
Figure 4b.
Figure 5a.
Effect on multi-unit activity of
lowering electrode in O.5mm.stages at
Ant.=8.0, Lat.=3.0.
Figure 5b.
Effect of raising electrode in O.5mm.
and 1.Omm. stages at Ant.=8.5, I..at.=l.O.
Figure 5c.
Effect of raising and lowering electrode
in O.5mm. stages in hypothalamus.
Lowering electrode to -2.Omm. caused a
drop in multi-unit activity at the
recording site of the stationary
electrode, perhaps because of destruction
of processes efferent to the recording
site.
Figure 5d.
Multi-unit activity change with 8.0mm.
shift of electrode into the posterior
hypothalamic area.
- 57 -
Figure 5a.
Figure 5b.
1
-
1
-.I.l:'
-;-.--,. .
-'-: ..
'
;:.-.:.."':..::-:'
.
.
_._.Y
__
1111a.1
Ant.=7.5
. H-
+
•
!....
Figure 5d.
Figure 5c.
Figure 6a.
Lateral hypothalamus.
Effect of Scc.
injection of 30% glucose-distilled
water.
The drop in activity level did
not recover during the recording session
in this case.
Figure 6b.
Lateral hypothalamus.
Transient effect
of Scc. injection of 30% glucose-distilled
water~
Figure 6c.
Lateral mammillary nucleus.
Effect of
Scc. injection of 30% glucose-distilled
water ..
Figure
6d~
Posterior hypothalamus.
Effect of Scc.
injection of 30% glucose-distilled water.
- 58 -
Figure 6a.
Figure 6b.
Figure 6c.
Figure 6d.
1 min.
Figure 7a.
Ventromedia1 hypothalamus.
Effect of Scc.
control injection of 25% saline solution.
The slight increase in mu1ti-unit activity
1eve1 during injection is characteristic
of most control injections of heavy saline
concentration with a11 recording sites.
This injection preceded that shown in
Fig. 7b.
Figure 7b.
Ventromedia1 hypothalamus.
Effect of Scc.
injection of 30% glucose-disti11ed water.
Figure
7c~
Ventromedia1 hypothalamus.
Effect of Scc.
control injection of 25% saline solution
given before injection shown in Figure 7d.
The drop in mu1ti-unit activity during and
just after saline injection occurred on1y
occassiona11y.
Figure 7d.
Ventromedial hypothalamus.
Effect of 5ec,
injection of 30% glucose-disti11ed water.
- 59 -
.
..•
Figure 7a.
..1..
..
.
.
.
.
•
Figure 7b.
,
,
,
,,.'
,,
'
. J_,
,-i
~_J_
III'
,,
.
~
.
Ho ..
..
10%
...
•
Figure 7c.
0
.
,,
R+,
• -~
1-0
Figure7d.
,
-
,
w
(of
-,
-
•
,
,
,
'~
LJ
!t.
'.
, "
,
%
Figure 8a.
Medial mammi11ary nucleus.
unit activity
chan~e
No mu1ti-
fo110wing Scc.
injection of 30% glucose-disti11ed
water.
Saline contro1s a1so had no
effect on activity 1eve1s.
Figure 8b.
Supramammi11ary decussation.
No mu1ti-
unit activity change fo110wing Scc.
injection of 30% glucose-disti11ed
water.
Saline contro1s simi1ar1y did
not affect activity at this locus.
- 60 -
1 min •
Figure 8a •
Figure 8b •
Figure 9a.
Lateral hypothalamus.
EEG amplitude
increase following Scc. injection of
30% glucose-distilled water.
Figure 9b.
Vemtromedial hypothalamus.
Slight EEG
frequency decrease following Scc.
injection of 30% glucose.
This decrease
was reliable but was always small.
Figure 9c.
Medial mammillary nucleus.
No EEG
response to Scc. injection of 30%
glucose-distilled water.
Figure 9d.
Lateral mammillary nucleus.
No EEG
response to Scc. injection of 30%
glucose-distilled water.
"
- 6L..:.
pre-injection
post-injection
Figure 9a.
pre-injection
Figure 9b.
pre-injection
5~t~A~\i~
"1\'~J"\"'fJ~',I'I,~\r--l-{t"'l'iJ~
se,c,
'
'.
!f~~:N\'J\~jl~'v1~'\~r.r.v-.\"'II~Y~~~\)Mj~f'\~~~\[~
\
;
post~injection
Figure 9c.
pre-injection
..,...n
post-injection
Figure 9d.
Figure 10a.
Lateral hypothalamus.
Infusion of 10%
glucose-saline started at arrow.
10%
saline control infusion previous to
arrow does not affect multi-unit activity.
Figure lOb.
Zona incerta.
Infusion of 10% glucose-
saline started at arrow.
10% saline
control infusion previous to arrow does
not affect multi-unit activity.
Figure 10c.
Posterior hypothalamus.
Sample record
of complete 10% glucose-saline infusion
started at first arrow and terminated
at second arrow, showing stable mu1tiunit activity levels during 10% saline
infusions before and after glucose
infusion.
See Fig. 13 for EEG recorded
during the same period.
Figure 10d.
Lateral mammillary nucleus.
Infusion
of 10% glucose-saline started at arrow.
10% saline control infusion previous to
arrow.
- 62 -
Figure 10a.
Figure lOb.
Figure lOc.
Figure lOd.
Figure lIa.
Ventromedial hypothalamus.
Infusion
of 10% glucose-saline started at arrow.
10% saline control infusion previous
to arrow does not affect multi-unit
activity.
Such increases typica1ly
level1ed off after a 10% to 20% increase
in activity level during glucose infusion.
Figure lIb.
Fields of Fore1/prerubra1 field area.
Infusion of 10% glucose-saline started
at arrow.
10% saline control infusion
previous to arrow does not affect mu1tiunit activity.
- 63 -
•
tU
y-f
y-f
QJ
~
-r-!
rz..
•
.0
y-f
y-f
QJ
~
or-!
rz..
.---,
Figure 12a.
Lateral hypothalamus.
Short-term,
peaked bursts occassiona11y seen in
mu1ti-unit activity during'10% glucose
infusion.
Figure 12b.
Later section of record shown in
Fig. 12a.
Infusion of 10% saline,
started at arrow, diminishes peaked
bursting phenomenon.
Figure 12c.
Posterior
~ypotha1amus.
Section of
record obtained during 10% saline
infusion after 10% glucose infusion.
Peaked drops in activity becoming
1ess frequent.
This effect continued
to dec1ine in frequency and fina11y
disappeared during subsequent glucose
infusion.
On1y one observation of
the phenomenon as made on the posterior
hypothalamus.
- 64 -
Figure 12a.
Figure 12b.
Figure 12e.
Figure l3a.
Posterior hypothalamus.
EEG during
infusion of 0.9% saline.
Figure l3b.
Same EEG during infusion of 10% glucosesaline approximately 15 minutes after
record shown in Fig. l3a and after 12
minutes of glucose infusion.
This
record was obtained during the first
portion of Figure 10c.
Figure l3c.
Same EEG after approximately 15 minutes
of 10% saline infusion following record
shown in Fig. l3b.
Figure 13d.
Same EEG after approxtmately 15 minutes
of 10% glucose-saline infusion following
record shown in Fig. l3c.
Figure l3e.
Same EEG after approximately 20 minutes
of 10% saline infusion following record
shown in Fig. 13d.
- 65 -
1 sec.
Figure 13a.
Figure 13b.
Figure 13c.
Figure 13d.
Figure 13e.
Figure l4a.
Vemtromedial hypothalamus.
amplitud~
Figure l4b.
EEG
increase with glucose infusion.
Ventramedial hypothalamus.
Amplitude
decrease with glucose infùsion.
Figure l4c.
Ventramedial hypothalamus.
Amplitude
decrease with glucose infusion.
Figure l4d.
Lateral hypothalamus.
No EEG response
to glucose infusion.
Figure l4e.
Lateral hypothalamus.
No EEG response
to glucose infusion.
Figure l4f.
Lateral hypothalamus.
No EEG response to
glucose infusion.
Figure l4g.
Lateral hypothalamus.
with glucose infusion.
Frequency increase
- 66 -
50uv 1
..__
1..,;;.0;-""
Top traces obtained during 10% saline control
infusions. Lower traces
obtained during 10% glucose infusions.
Figure 14a.
50uv 1 1 sec.
Figure 14b.
50UVI
1 sec.
50uvl
1 sec.
Figure 14c.
50uvl
1 sec.
--------Figure 14d.
50uvl
1 sec,
Figure 14f.
Figure 14e.
50uvl 1 sec.
Figure 14g.
Figure l5a.
Fields of Foreljprerubral field.
EEG
amplitude,and frequency increases with
10% glucose-saline infusion.
Figure l5b.
Ventral posteromedial nucleus.
EEG
amplitude increase with 10% glucosesaline infusion.
Figure l5c.
Anterior hypothalamic area.
Slight
frequency decrease with 10% glucosesaline infusion.
The apparent amplitude
increase does not persist in the record
shown here, and did not occur during
other infusions, although the frequency
decrease was reliable in the one preparation
tested at this site.
- 67 -
10% saline
50UV
_ _....l~s~ec:i.a.I
••1
10% glucose
Figure 15a •
10% saline
1 sec.1 50uv
10% glucose
Figure 15b.
10% saline
50UV
_ _ _l..;;.s~e;.c.:.
• .J.1
10% glucose
Figure 15c.